Supplementary Table S1: iNMF cluster defining genes found in the TCGA dataset. Column 1 indicates genes found by iNMF to define the clusters specified in column 2. Supplementary Table S2: iNMF cluster defining genes in the GSE8894 validation data set. Column 1 indicates genes found by iNMF to define the clusters specified in column 2. Supplementary Table S3: Cell Line IC50 Values. Indicates the individual IC50 values and the cluster IC50 values used to calculate the compound sensitivity score shown in Table 1. Supplementary Table S4: Gene Set Enrichment Analysis (GSEA) results. Gene set enrichment scores for TCGA and cell lines are indicated. Supplementary Table S5: Differential microRNA expression values. This table indicates microRNAs that were differentially expressed between the three subtypes in TCGA and cell lines as defined by an ANOVA test with a cutoff of p<0.05. p-values and q-values for each microRNA are shown. Supplementary Table S6: Transcription Factor Master List. T-tests were performed on expression of transcription factors predicted to bind to microRNA promoters. Transcription factors that showed statistically significant p<0.05 expression between two clusters are highlighted in green. The clusters that are being compared are indicated by the “Level” and “-Level” columns. Supplementary Table S7: microRNA expression after ETS1 knockdown. R-squared values for correlation between ETS1 and each microRNA are shown for both TCGA and cell lines are indicated. In addition the results of t-tests performed on fold change expression data after ETS1 knockdown for the data presented in Figure 4 are shown. Statistically significant results (p<0.05) are highlighted in green. Supplementary Table S8: Differentially methylated genes. List of genes identified by iNMF to be differentially expressed between clusters that are also differentially methylated between clusters. The gene name, the cluster, and the p-values are indicated. Supplementary Table S9: Gene expression changes after TET1 knockdown. The difference, standard error, and t-test results for mRNA changes after TET1 knockdown in LK2 and NCIH520 cells are shown by gene name. Supplementary Table S10: Gene expression changes after gefitinib treatment. The difference, standard error, and t-test results for mRNA changes after EBC1 and SKMES1 cell lines were treated with gefitinib are shown. Significant (p<0.05) changes are highlighted in green. Supplementary Table S11: Primers and Probes. Listed are the primers and probes used for expression analysis. Supplementary Table S12: Antibodies. Listed are the antibodies used for western blots.